a phase 1/2/3 study of ux701 gene therapy in adults with wilson disease

Conditions: Wilson Disease

Summary: the primary objectives of this study are to evaluate the safety of single iv doses of ux701 in patients with wilson disease, to select the ux701 dose with the best benefit/risk profile based on the totality of safety and efficacy data and to evaluate the effect of ux701 on copper regulation.

stage 1 (phase 1/2) is an open-label safety and dose-finding stage designed to evaluate the safety and efficacy of 4 dose levels of ux701 to establish initial safety of ux701 and select a safe and efficacious dose for further evaluation. stage 2 (phase 3) is a randomized, open-label, active-controlled stage to evaluate the safety and efficacy of ux701 using the dose selected in stage 1. stage 3 is a long-term follow-up stage designed to evaluate the safety, efficacy, and clinical benefit of ux701 for at least 5 years from the time of ux701 administration. participants who receive ux701 will receive premedication, prophylactic oral corticosteroids and immunomodulation therapy.

Eligibility criteria:
key inclusion criteria: * confirmed diagnosis of wilson disease based on genetic confirmation of heterozygous or homozygous biallelic atp7b mutation. * stable wilson disease as evidenced by ongoing copper chelator (ie, penicillamine, trientine) and/or zinc therapy for at least 2 months at screening, with no medication or dose changes for at least 2 months at screening. * ongoing restriction of high copper containing foods for at least 2 months at screening and continued through study participation. * willing and able to comply with all study procedures and requirements, including frequent blood collection, total urine collection over a 24-hour period, patient-reported outcome assessments, and long-term follow-up key exclusion criteria: * detectable pre-existing antibodies to the aav9 capsid. * stage 1 only: history of copper chelator or zinc therapy noncompliance, in the investigator's judgment, within 6 months prior to screening. * history of liver transplant. * active decompensated hepatic cirrhosis or history of hepatic encephalopathy. * significant hepatic inflammation as evidenced by laboratory abnormalities. * model for end-stage liver disease (meld) score \> 13. * hemoglobin \< 9 g/dl * presence of stage 3 or higher chronic kidney disease based on estimated glomerular filtration rate \< 60 ml/min/1.73 m2. * marked neurological deficit or compromise that, in the investigator's opinion, would interfere with the subject's safety or ability to participate in the study. * moderate to severe depression, recent or active suicidal ideation with intent or suicidal behavior, psychosis, or unstable psychiatric illness. * known hypersensitivity to ux701 or its excipients, copper chelators, zinc, rituximab, tacrolimus, corticosteroids, or eculizumab that, in the investigator's judgement, places the participant at increased risk for adverse events. * participation in another gene transfer study or use of another gene transfer product before or during study participation. * subjects with known hypersensitivity to amide-containing local anesthetics are excluded from participating in the optional liver biopsy substudy. note: other protocol defined inclusion/ exclusion criteria may apply